The present invention comprises an approach for calibrating the sensitivity to polarization, optics degradation, spectral and stray light response functions of instruments on orbit. The concept is based on using an accurate ground-based laser system, Ground-to-Space Laser Calibration (GSLC), transmitting laser light to instrument on orbit during nighttime substantially clear-sky conditions. To minimize atmospheric contribution to the calibration uncertainty the calibration cycles should be performed in short time intervals, and all required measurements are designed to be relative. The calibration cycles involve ground operations with laser beam polarization and wavelength changes.